The many faces of the SOCS box.
The suppressors of cytokine signalling (SOCS) box is a structural domain found at the C-terminus of over 70 human proteins. It is usually coupled to a protein interaction module such as an SH2 domain in case of SOCS proteins, a family of modulators of cytokine signaling. The SOCS box participates in the formation of E3 ligase complexes, marking activated cytokine receptor complexes for proteasomal degradation. A similar mechanism was recently uncovered for controlling SOCS activity itself, since SOCS2 was found to enhance the turnover of other SOCS proteins. The SOCS box can also add unique features to individual SOCS proteins: it can function as an adaptor domain as was demonstrated for SOCS3, or as a modulator of substrate binding in case of CIS. In this review we discuss these multiple roles of the SOCS box, which emerges as a versatile module controlling cytokine signaling via multiple mechanisms.
Piessevaux
Julie
J
Department of Medical Protein Research, VIB, Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, Belgium. julie.piessevaux@ugent.be
Lavens
Delphine
D
Peelman
Frank
F
Tavernier
Jan
J
D006801:Humans; D017434:Protein Structure, Tertiary; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D050826:Suppressor of Cytokine Signaling Proteins / Q000737:chemistry / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination / Q000502:physiology
D050796:STAT3 Transcription Factor; D050826:Suppressor of Cytokine Signaling Proteins; D044767:Ubiquitin-Protein Ligases